Vision information is recognized when the light enters through the cornea, which is a transparent tissue at the front of the eye ball, reaches the retina to excite the retinal nerve cell that generates electric signals, which are transmitted to the cerebral visual area via the optic nerve. Good eyesight requires a transparent cornea. The transparency of the cornea is maintained since the pump function and barrier function of the corneal endothelial cell keep a constant water content.
The corneal endothelial cell density is about 3000 cells/mm2 in human at birth. The cell has no ability to regenerate after damage. In endothelial corneal dystrophy and bullous keratopathy caused by functional disorder of corneal endothelium due to various etiologies, the corneal edema and opacity occur to markedly decrease vision. At present, penetrating keratoplasty for transplanting the whole three-layer structure of corneal epithelium, stroma and endothelium is performed for bullous keratopathy. However, corneal donation in Japan is insufficient, and the number of waiting patients for corneal transplantation is about 5500, but the number of corneal transplantation domestically performed per year is about 2700.
In an attempt to reduce the risk of rejection and postoperative complications, and acquire better visual function, the idea of “parts transplantation” for transplanting only the disordered tissue is attracting attention in recent years. Among the corneal transplantations, an epithelium transplantation procedure in which only the corneal epithelium is transplanted, an epithelium transplantation procedure of cultured oral mucous membrane in which mucous membrane is transplanted instead of the corneal epithelium, a procedure of deep layer and superficial layer corneal transplantation in which stromal tissue is transplanted, and the like have been performed. A method of transplanting only the corneal endothelium is under consideration. For transplantation of corneal endothelium, a corneal endothelium-like sheet comprising a corneal endothelial layer cultured on a collagen layer is known (see patent references 1 and 2). These sheets are expected to replace only the disordered endothelial cell layer with healthy endothelial cells by transplanting and supplementing corneal endothelium cultured in vitro, instead of penetrating keratoplasty performed heretofore for corneal endothelial diseases. However, since corneal endothelial cell is considered to have no ability to proliferate in vivo, a sufficient number of cultured cells are required to cover the area necessary for transplantation.
patent reference 1: JP-A-2004-24852
patent reference 2: JP-A-2005-229869